Nitric oxide and homeostatic control: an intercellular signalling molecule contributing to autonomic and neuroendocrine integration?

Accumulated evidence indicates that nitric oxide (NO) plays a pivotal role in the central control of bodily homeostasis, including cardiovascular and fluid balance regulation. Two major neuronal substrates mediating NO actions in the control of homeostasis are the paraventricular nucleus (PVN) of the hypothalamus, considered a key center for the integration of neuroendocrine and autonomic functions, and the supraoptic nucleus (SON). In this work, a comprehensive review of NO modulatory actions within the SON/PVN, including NO actions on neuroendocrine and autonomic outputs, as well as the cellular mechanisms underlying these effects is provided. Furthermore, this review comprises recent progress from our laboratory that adds to our current understanding of the cellular sources, targets and mechanisms underlying NO actions within neuroendocrine and autonomic hypothalamic neuronal circuits. By combining in vitro patch clamp recordings, tract-tracing neuroanatomy, immunohistochemistry and live imaging techniques, we started to shed light into the cellular sources and signals driving NO production within the SON and PVN, as well as NO actions and mechanisms targeting discrete neuronal populations within these circuits. Based on this new information, we have expanded one of the current working models in the field, highlighting a key role for NO as a signaling molecule that facilitates crosstalk among various cell types and systems. We propose that this dynamic NO signaling mechanisms may constitute a neuroanatomical and functional substrate underlying the ability of the SON and PVN to coordinate complex neuroendocrine and autonomic output patterns.